Parkinson's disease (PD) is a progressive neurodegenerative disease, primarily of the substantia nigra in the basal ganglia, that causes resting tremor, bradykinesia, rigidity, postural instability, and gait impairment. PD affects about 1% of the population older than 60 years. It was known to be associated with increased mortality rates, physical disability, non-motor symptoms, and impaired health-related quality of life compared with the quality of life of individuals without PD (Bennett DA, et al., 1996, N Engl J Med 334(2): 71-76; Louis ED, et al., 1997, Arch Neurol 54(3): 260-264).
Conventional Magnetic Resonance imaging (MRI) characteristics of the substantia nigra in PD include increased iron-related contrast enhancement (Gorell J M, et al., 1995, Neurology 45 (6):1138-1143) and loss of signal intensity in the lateral portion of the substantia nigra (Minati L, et al., 2007, AJNR Am J Neuroradiol 28(2): 309-313). Although there has been notable progress in studying the correlates of nigral degeneration by means of Magnetic Resonance imaging, techniques that enable accurate differentiation between patients with PD and control subjects remain elusive.
Conventional diffusion coefficients calculated by using the Stejskal-Tanner equation (Stejskal E O, Tanner JE, 1965, J Chem Phys 42(1): 288-292) are based on the assumption in a free and unrestricted medium. However, living tissues are known to be heterogeneous in nature and to comprise of multiple compartments. For these reasons, Diffusion Tensor imaging was proposed to measure the directional dependence of in vivo diffusion and was found to be successful. This technique has been shown to be clinically useful in the detection of white matter diseases (Rose SE, et al. 2000, J Neurol Neurosurg Psychiatry 69(4): 528-530; Werring DJ, et al., 1999, Neurology 52(8): 1626-1632).
In general, water diffusion in living tissue is hindered by interactions with other molecules and cell membranes. Therefore, water in biologic structures often displays non-Gaussian diffusion behavior. MR diffusion kurtosis imaging has been recently proposed as a means of quantifying non-Gaussian water diffusion (Jensen J H, Helpern JA, 2003, Berkeley, Calif.: International Society for Magnetic Resonance in Medicine, 2154; Jensen J H, et al., 2005, Magn Reson Med 53(6): 1432-1440; Jensen J H, Helpern J A, 2010, NMR Biomed 23(7): 698-710). Diffusion Kurtosis is a dimensionless measure of water diffusion as deviated from Gaussian distribution and reflects the changes in structural complexity. The kurtosis of water diffusion has been shown to be altered in different conditions that affect the central nervous system, including malignancy (Raab P, et al., 2010, Radiology 254(3): 876-881) and age-related degeneration (Jensen J H, et al., 2008, J Magn Reson Imaging 28 (6): 1345-1350).
Previous studies have shown the feasibility of using the changes of Diffusion Tensor imaging to investigate neuronal loss in different neurodegenerative diseases (Pfefferbaum A, et is al., 2000, Magn Reson Med 44(2): 259-268; Wang J J, et al., 2010, J Magn Reson Imaging 32(1): 69-75). However, the diffusion tensor imaging findings of Parkinson Disease are controversial (Vaillancourt, D. E., et al., 2009, Neurology 72(16): p. 1378; Chan, L. L., et al., 2007, Journal of Neurology, Neurosurgery & Psychiatry. 78(12): p. 1383-1468). A precise diffusion model for the gray matter in general and the basal ganglia in particular has not yet been established (Wang J J, et al., 2010, ut supra). Our study results demonstrate that diffusion kurtosis imaging in the basal ganglia can improve the MR based diagnosis of PD.